Laser spectroscopic instrumentation for isotopic sensing of biogenic Nitric Oxide

用于生物一氧化氮同位素传感的激光光谱仪器

• 批准号: 7943860
• 负责人: Gerard Wysocki
• 金额: $ 19.17万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7943860
• 关键词: Accident and Emergency department; Accounting; Agreement; American; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Asthma; Biochemical Process; Biological; Biological Markers; Biological Process; Biology; Biopsy; Brain; Breath Tests; Breathing; Bronchodilator Agents; Calibration; Carbon Dioxide; Cardiovascular system; Cells; Chemistry; Chest; Child; Chronic; Clinical Research; Complex; Concentration measurement; Data Reporting; Dependence; Detection; Development; Diagnosis; Diagnostic; Disease; Distal; Enzymes; Epithelial Cells; European; Exhalation; Exhibits; Free Radicals; Gases; Goals; Health; Home environment; Hospitals; Host Defense; Human; Immunity; Individual; Inflammation; Inflammatory; Inflammatory Response; Injury; Investigation; Isotope Labeling; Isotopes; Kinetics; Laboratories; Lasers; Lead; Letters; Life; Lower respiratory tract structure; Lung; Lung Inflammation; Lung diseases; Maintenance; Malignant neoplasm of lung; Mammalian Cell; Measurable; Measurement; Measures; Mediating; Medical; Medicine; Metabolism; Methods; Minor; Molecular; Monitor; Muscle; Nasal cavity; Nitric Oxide; Nobel Prize; Nose; Obstruction; Operative Surgical Procedures; Optics; Organ Transplantation; Outpatients; Oxidants; Pathogenesis; Patients; Perception; Performance; Peroxonitrite; Persons; Pharmaceutical Preparations; Physicians; Physiological Processes; Physiology; Play; Pollution; Preparation; Prevention; Process; Property; Public Health; Publications; Publishing; Pulmonary Hypertension; Pulmonary function tests; Reaction Time; Regulation; Reliance; Reporting; Research; Resolution; Respiration Disorders; Role; Rotation; Sampling; Science; Scientist; Sensitivity and Specificity; Signaling Molecule; Societies; Source; Specificity; Spectrum Analysis; Spirometry; Sudden Death; Swelling; Symptoms; System; Techniques; Technology; Testing; Time; Tube; United States; Visit; Water; airway hyperresponsiveness; airway inflammation; antimicrobial; asthmatic patient; bactericide; base; blood pressure regulation; constriction; cytotoxic; cytotoxicity; design; dosage; effective therapy; exhaust; flexibility; frontier; gas analyzer; heterodyning; improved; instrument; instrumentation; interest; neoplastic cell; new technology; novel; operation; physical conditioning; portability; prototype; public health relevance; quantum; respiratory; stable isotope; user-friendly

DESCRIPTION (provided by applicant): Detection of nitric oxide is of great importance in a number of bio-medical applications such as non-invasive medical diagnostics based on exhaled human breath analysis or study of the regulation of biological and physiological processes in human and mammalian cells. None of currently available NO sensing technologies can simultaneously provide sub-parts-per- billion sensitivity, <0.1-sec time resolution, capability of selective measurements of NO isotopes, no sample preparation, and high immunity to interferences from other molecular species in a single, compact, portable and user-friendly instrument. The research proposed in this project will lead to development of a novel laser spectroscopic sensing instrumentation, which will provide unique capabilities of biogenic NO quantification. The new technology will be based on Faraday rotation spectroscopy, which can provide unprecedented sensitivity and specificity to NO. To achieve the goals for the system performance and a compact footprint a novel sensitivity enhancement based on ultra-sensitive optical heterodyne detection will be implemented. A broadly tunable mid-infrared external cavity quantum cascade laser will be used as a spectroscopic source, which will provide capability of quantification of all stable NO isotopes with a single instrument. The specific aims of the proposed project are: 1. Development and laboratory demonstration of a novel laser based, optical heterodyne Faraday rotation spectroscopic system for detection of all stable isotopes of NO in exhaled human breath with sub-ppb sensitivity, sub-second resolution and high specificity to discriminate against potentially interfering gases, particularly H2O and CO2. 2. Development, laboratory tests and implementation of reliable consumable-free calibration techniques, which will provide automatic and maintenance-free operation of the instrument. 3. Design and prototype development of a portable sensing instrument with sensitivity, selectivity and fast response time required for exhaled NO concentration measurements in both single breath maneuver as well as during tidal breathing. The technology developed during this project will be broadly applicable to breath analysis as well as other bio-medical applications. In addition other non-biomedical applications such as atmospheric pollution monitoring, combustion diagnostics and vehicle exhaust monitoring that indirectly but significantly help improving people's health will benefit from the proposed development of laser based gas analyzer technology. PUBLIC HEALTH RELEVANCE: Project Narrative Nitric oxide plays a major role in a number of biological processes such as indication of airway inflammation, regulation of blood pressure, regulation of fundamental cellular activities such as whether cells live or die, or can even change the computational ability of the brain. Therefore better understanding of the mechanisms by which nitric oxide contributes to the process biology and bio-chemistry can significantly enhance understanding of many types of diseases or injuries and will result in improved detection, prevention or treatment methods. The proposed research will provide doctors and scientists with a novel nitric oxide sensing instrumentation that will outperform technologies currently used in clinical studies, and will allow for significant advancements in bio-medical science and for improvements of public health.

描述（由申请人提供）：一氧化氮的检测在许多生物医学应用中非常重要，例如基于人类呼出气体分析的非侵入性医学诊断或人类和哺乳动物生物和生理过程调节的研究细胞。目前可用的 NO 传感技术都无法同时提供十亿分之一的灵敏度、<0.1 秒的时间分辨率、选择性测量 NO 同位素的能力、无需样品制备以及对其他分子种类干扰的高免疫力。 、紧凑、便携且用户友好的仪器。该项目提出的研究将导致新型激光光谱传感仪器的开发，该仪器将提供生物一氧化氮定量的独特功能。新技术将基于法拉第旋转光谱，它可以为 NO 提供前所未有的灵敏度和特异性。为了实现系统性能和紧凑占地面积的目标，将实施基于超灵敏光学外差检测的新颖灵敏度增强。广泛可调的中红外外腔量子级联激光器将用作光谱源，这将提供用一台仪器量化所有稳定 NO 同位素的能力。拟议项目的具体目标是： 1. 开发和实验室演示一种新型激光光学外差法拉第旋转光谱系统，用于检测人类呼出气体中所有稳定的 NO 同位素，灵敏度亚 ppb、亚秒分辨率和高特异性，可区分潜在干扰气体，特别是 H2O 和 CO2。 2. 可靠的无耗材校准技术的开发、实验室测试和实施，这将提供仪器的自动和免维护操作。 3. 便携式传感仪器的设计和原型开发，具有单次呼吸操作和潮式呼吸期间呼出一氧化氮浓度测量所需的灵敏度、选择性和快速响应时间。该项目开发的技术将广泛适用于呼吸分析以及其他生物医学应用。此外，其他非生物医学应用，如大气污染监测、燃烧诊断和汽车尾气监测，间接但显着地帮助改善人们的健康，也将受益于基于激光的气体分析技术的拟议开发。 公共健康相关性：项目叙述一氧化氮在许多生物过程中发挥着重要作用，例如气道炎症的指示、血压的调节、基本细胞活动的调节（例如细胞的存活或死亡），甚至可以改变计算能力大脑的。因此，更好地了解一氧化氮对生物学和生物化学过程的贡献机制可以显着增强对许多类型的疾病或损伤的理解，并将导致改进的检测、预防或治疗方法。拟议的研究将为医生和科学家提供一种新型的一氧化氮传感仪器，其性能将优于目前临床研究中使用的技术，并将促进生物医学科学的重大进步和改善公共卫生。